ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.4456A>C (p.Met1486Leu) (rs199473258)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058675 SCV000090195 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Invitae RCV000797581 SCV000937145 uncertain significance Brugada syndrome 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 1487 of the SCN5A protein (p.Met1487Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual referred for long QT syndrome testing (PMID: 19716085) and in an individual who suffered sudden unexplained death (PMID: 29247119). ClinVar contains an entry for this variant (Variation ID: 67895). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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